rs2523607

Variant names:

• chr6-31355013-T-A
• rs2523607
• NM_005514.8:c.1012+94A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31355013-T-A
• chr6-31355013-T-C
• chr6-31355013-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005514.8(HLA-B):​c.1012+94A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.084 (617 hom., cov: 8)
  • Exomes 𝑓: 0.11 (5626 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 38 publications found

Genes affected

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

ENSG00000298396 (HGNC:):

MIR6891 (HGNC:50243): (microRNA 6891) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.1012+94A>T		intron_variant	Intron 5 of 7	ENST00000412585.7	NP_005505.2
MIR6891	NR_106951.1	n.*211A>T		downstream_gene_variant
MIR6891	unassigned_transcript_1096	n.*215A>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7	c.1012+94A>T		intron_variant	Intron 5 of 7	6	NM_005514.8	ENSP00000399168.2

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 5259 AN: 62516 Hom.: 614 Cov.: 8

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.00294

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0426

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.0773

GnomAD4 exome AF: 0.106 AC: 33241 AN: 313138 Hom.: 5626 Cov.: 4 AF XY: 0.106 AC XY: 17662 AN XY: 165856

African (AFR) AF: 0.128 AC: 981 AN: 7688

American (AMR) AF: 0.0455 AC: 766 AN: 16826

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 835 AN: 8362

East Asian (EAS) AF: 0.00176 AC: 27 AN: 15314

South Asian (SAS) AF: 0.113 AC: 2941 AN: 25968

European-Finnish (FIN) AF: 0.0802 AC: 1812 AN: 22594

Middle Eastern (MID) AF: 0.142 AC: 177 AN: 1246

European-Non Finnish (NFE) AF: 0.119 AC: 23701 AN: 199010

Other (OTH) AF: 0.124 AC: 2001 AN: 16130

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0842 AC: 5267 AN: 62530 Hom.: 617 Cov.: 8 AF XY: 0.0792 AC XY: 2364 AN XY: 29844

African (AFR) AF: 0.0825 AC: 1058 AN: 12828

American (AMR) AF: 0.0499 AC: 236 AN: 4730

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 145 AN: 1740

East Asian (EAS) AF: 0.00295 AC: 7 AN: 2372

South Asian (SAS) AF: 0.0663 AC: 77 AN: 1162

European-Finnish (FIN) AF: 0.0629 AC: 284 AN: 4514

Middle Eastern (MID) AF: 0.0435 AC: 4 AN: 92

European-Non Finnish (NFE) AF: 0.0983 AC: 3332 AN: 33904

Other (OTH) AF: 0.0761 AC: 53 AN: 696

Alfa AF: 0.0537 Hom.: 61

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.50
PhyloP100		-1.5
PromoterAI		-0.0096	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2523607; hg19: chr6-31322790;